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镉相关基因在肝癌中的鉴定和特征分析。

Identification and Characterization of Cadmium-Related Genes in Liver Carcinoma.

机构信息

College of Food Science and Nutritional Engineering, China Agriculture University, Beijing, China.

Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.

出版信息

Biol Trace Elem Res. 2018 Apr;182(2):238-247. doi: 10.1007/s12011-017-1106-z. Epub 2017 Aug 8.

Abstract

Evidence indicates that exposure to heavy trace element might be a risk factor for liver carcinoma. Cadmium has been supposed to be a carcinogen that has a correlation with the risk of a number of cancers, including liver cancer. However, the mechanisms underlying Cadmium-induced malignant transformation in liver cells are not fully understood. In the present study, we aimed to screen the differentially expressed genes (DEGs) that might play a role in both the Cadmium-related liver cell transformation and the development of liver cancer. Microarray-based gene expression profiles concerning liver carcinoma vs non-cancerous tissue (GSE64041) and Cadmium-treated liver cells vs controls (GSE8865 and GSE31286), respectively, were retrieved from Gene Expression Omnibus (GEO) database. Then, DEGs of each profile were calculated and screened. The intersection of each DEGs was obtained by Venn analysis. Afterwards, the possible roles of the selected genes in cancer development were evaluated by using Oncomine database and TCGA cohort analysis. Consequently, three DEGs, LRAT, SLC7A11, and ITGA2, were selected for further analysis. SLC7A11 and ITGA2, but not LRAT, were upregulated in liver cancer compared with those in normal tissues, respectively. After using a TCGA cohort analysis, results failed to show a significant correlation between SLC7A11 or ITGA2 expression and clinical parameters. However, the survival analysis showed that patients with high expression levels of SLC7A11 had a shorter overall survival time relative to those of the patients with low levels. In conclusion, SLC7A11 and ITGA2 might play a role in the Cadmium-induced liver cell damage or transformation, and the development of liver carcinoma. SLC7A11 might be a prognostic factor for patients with liver carcinoma. Future validation experiments are needed to verify the results.

摘要

证据表明,接触重金属元素可能是肝癌的一个风险因素。镉被认为是一种致癌物质,与包括肝癌在内的多种癌症的风险有关。然而,镉诱导肝细胞恶性转化的机制尚不完全清楚。在本研究中,我们旨在筛选可能在镉相关的肝细胞转化和肝癌发展中起作用的差异表达基因(DEGs)。从基因表达综合数据库(GEO)中分别检索了肝癌与非癌组织(GSE64041)和镉处理的肝细胞与对照(GSE8865 和 GSE31286)的基于微阵列的基因表达谱,然后计算并筛选每个谱的 DEGs。通过 Venn 分析获得每个 DEGs 的交集。之后,使用 Oncomine 数据库和 TCGA 队列分析评估所选基因在癌症发展中的可能作用。结果,选择了三个 DEGs,LRAT、SLC7A11 和 ITGA2,进行进一步分析。与正常组织相比,SLC7A11 和 ITGA2 在肝癌中上调,而 LRAT 则没有。使用 TCGA 队列分析后,结果未能显示 SLC7A11 或 ITGA2 表达与临床参数之间存在显著相关性。然而,生存分析显示,SLC7A11 表达水平高的患者的总生存时间相对较短。综上所述,SLC7A11 和 ITGA2 可能在镉诱导的肝细胞损伤或转化以及肝癌的发生中发挥作用。SLC7A11 可能是肝癌患者的预后因素。需要进一步的验证实验来验证这些结果。

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